The spectrum of infectious complications after hematopoietic stem cell transplantation (HSCT) has been markedly altered in the last decade. Early ganciclovir therapy has reduced CMV infection but its hematopoietic toxicity limits its use, and the lack of immune reconstitution to CMV, especially among those with GVHD, has resulted in a high incidence of CMV reactivation disease late after transplant. Also, while fluconazole prophylaxis has markedly reduced invasive candidal infections, the incidence of aspergillosis has tripled. Most cases now occur in the nonneutropenic, but highly immunosuppressed host, illustrating the potential importance of T cell immunity in this entity. Subclinical primary CMV infection (i.e., acquisition of CMV infection below the threshold of current antigenemia assays) in CMV seronegative recipients of a seropositive donors (D+R-) appears to be a newly identified risk factor for the acquisition of pulmonary aspergillosis and invasive bacterial infections. The specific aims of the project are: Specific Aim 1. To reduce the morbidity and mortality of late onset CMV disease after HSCT. A randomized double-blind study will be performed to examine whether valganciclovir will prevent late onset CMV disease without increased CMV resistance or further delay in CMV immune reconstitution. Specific Aim 2. To determine the role of T cell mediated immunity in the development and outcome of post-engraftment aspergillosis. CD4+ and CD8+ T cell responses to A. fumigatus antigens and neutrophil anti-hyphal activity will be assessed longitudinally in allogeneic HSCT recipients to define whether those with altered responses are at greater risk of infection and poor outcome. Studies to define responses to purified antigen preparations will be initiated.